Closing the Gap between the Auditory Nerve and Cochlear Implant Electrodes: Which Neurotrophin Cocktail Performs Best for Axonal Outgrowth and Is Electrical Stimulation Beneficial?

Article Article scientifique Article Closing the Gap between the Auditory Nerve and Cochlear Implant Electrodes: Which Neurotrophin Cocktail Performs Best for Axonal Outgrowth and Is Electrical Stimulation Beneficial? eng 2023-01-19 2023-01-19 author Schmidbauer Dominik 0000-0001-7913-9221 author Podobrin Stefanie Barbara 0000-0002-7938-9869 56965 author Rousset Francis 0000-0001-7747-179X 819901 Département des neurosciences cliniques (OTONO) author Löwenheim Hubert author Senn Pascal 0000-0002-4619-3341 822485 Département des neurosciences cliniques (OTONO) author Glueckert Rudolf 0000-0002-2900-6866 2013 10.3390/ijms24032013 36768339 1422-0067 PMC9916558 https://www.mdpi.com/1422-0067/24/3/2013 Neurotrophins promote neurite outgrowth of auditory neurons and may help closing the gap to cochlear implant (CI) electrodes to enhance electrical hearing. The best concentrations and mix of neurotrophins for this nerve regrowth are unknown. Whether electrical stimulation (ES) during outgrowth is beneficial or may direct axons is another open question. Auditory neuron explant cultures of distinct cochlear turns of 6–7 days old mice were cultured for four days. We tested different concentrations and combinations of BDNF and NT-3 and quantified the numbers and lengths of neurites with an advanced automated analysis. A custom-made 24-well electrical stimulator based on two bulk CIs served to test different ES strategies. Quantification of receptors trkB, trkC, p75<sup>NTR</sup>, and histological analysis helped to analyze effects. We found 25 ng/mL BDNF to perform best, especially in basal neurons, a negative influence of NT-3 in combined BDNF/NT-3 scenarios, and tonotopic changes in trk and p75<sup>NTR</sup> receptor stainings. ES largely impeded neurite outgrowth and glia ensheathment in an amplitude-dependent way. Apical neurons showed slight benefits in neurite numbers and length with ES at 10 and 500 µA. We recommend BDNF as a potent drug to enhance the man-machine interface, but CIs should be better activated after nerve regrowth. Cochlear implant Electrical stimulation Nerve regeneration Neurotrophin treatment Spiral ganglion Dewey 616.8 Dewey 616.07 61 Département des neurosciences cliniques 226 137 Département de pathologie et immunologie 21F false 948 Groupe Pascal Senn 954 International journal of molecular sciences 24 3 87178fdd-aab8-4652-8fd0-ab2791265b9f Article (Published version) Public Article-scientifique-from-crossref.pdf 6324091 application/pdf CC BY-4.0 7c33b913d6ed837befbd106db48fae9001a2321161566794ad439199c2d36257 33aa025a-c758-4967-a666-2dce9725c3b1 Appendix Public ijms-2098138-suppl-FigureS1.pdf 449789 application/pdf Figure S1 72cf050bc56c679d05a47c7dc5c2e5ca912b32d3c13d41172e96dd590ac635eb e2e190ac-71bd-4f0b-bf4e-277e556da3e7 Recording Public Supplementary video.mp4 83882884 video/mp4 Supplementary video 4ef75d936f92a159c96f18d11448dffcc431d5c46cd30f71b6908c66ebdd69ea openAccess Faculté de médecine / Section de médecine clinique / Département des neurosciences cliniques Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Closing the Gap between the Auditory Nerve and Cochlear Implant Electrodes: Which Neurotrophin Cocktail Performs Best for Axonal Outgrowth and Is Electrical Stimulation Beneficial?	International journal of molecular sciences			2023	118	46

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Podobrin, Stefanie Barbara